title: SHIV-1157i and passaged progeny viruses encoding R5 HIV-1 clade C env cause AIDS in rhesus monkeys.
abstract: BACKGROUND
  Infection of nonhuman primates with simian immunodeficiency virus (SIV) or chimeric simian-human immunodeficiency virus (SHIV) strains is widely used to study lentiviral pathogenesis, antiviral immunity and the efficacy of AIDS vaccine candidates. SHIV challenges allow assessment of anti-HIV-1 envelope responses in primates. As such, SHIVs should mimic natural HIV-1 infection in humans and, to address the pandemic, encode HIV-1 Env components representing major viral subtypes worldwide.
  
  
  RESULTS
  We have developed a panel of clade C R5-tropic SHIVs based upon env of a Zambian pediatric isolate of HIV-1 clade C, the world's most prevalent HIV-1 subtype. The parental infectious proviral clone, SHIV-1157i, was rapidly passaged through five rhesus monkeys. After AIDS developed in the first animal at week 123 post-inoculation, infected blood was infused into a sixth monkey. Virus reisolated at this late stage was still exclusively R5 tropic and mucosally transmissible. Here we describe the long-term follow-up of this initial cohort of six monkeys. Two have remained non-progressors, whereas the other four gradually progressed to AIDS within 123-270 weeks post-exposure. Two progressors succumbed to opportunistic infections, including a case of SV40 encephalitis.
  
  
  CONCLUSIONS
  These data document the disease progression induced by the first mucosally transmissible, pathogenic R5 non-clade B SHIV and suggest that SHIV-1157i-derived viruses, including the late-stage, highly replication-competent SHIV-1157ipd3N4 previously described (Song et al., 2006), display biological characteristics that mirror those of HIV-1 clade C and support their expanded use for AIDS vaccine studies in nonhuman primates.
authors.affiliation: Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. michael_humbert@dfci.harvard.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Humbert
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rasmussen
authors.forename: Ruijiang
authors.initials: R
authors.lastname: Song
authors.forename: Helena
authors.initials: H
authors.lastname: Ong
authors.forename: Prachi
authors.initials: P
authors.lastname: Sharma
authors.forename: Agnès L
authors.initials: AL
authors.lastname: Chenine
authors.forename: Victor G
authors.initials: VG
authors.lastname: Kramer
authors.forename: Nagadenahalli B
authors.initials: NB
authors.lastname: Siddappa
authors.forename: Weidong
authors.initials: W
authors.lastname: Xu
authors.forename: James G
authors.initials: JG
authors.lastname: Else
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Novembre
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Strobert
authors.forename: Shawn P
authors.initials: SP
authors.lastname: O'Neil
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Ruprecht
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology / Q000635:transmission* / Q000821:virology; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D012692:Serial Passage; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology / Q000635:transmission* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism; D019562:Viral Load; D014779:Virus Replication
chemical_list: D014759:Viral Envelope Proteins